Altered hypothalamic-pituitary axis responsiveness is found in a variety of human diseases. The pituicyte's hormone receptor number determines, in part, the magnitude of its response to hypothalamic peptides. The proposed research will test the hypothesis that modulation of receptor biosynthesis contributes to the control of receptor number. Initially, the regulation of anterior pituitary receptor synthesis will be studied with a functional bioassay of mRNA activity based on Xenopus oocyte expression. The well-characterized models of AVP and TRH receptor regulation in the pituitary will be studied. The effect of adrenalectomy and corticosteroids on AVP receptor mRNA activity will be measure. The impact of thyroxine, estradiol and a TRH analog on TRH receptor mRNA activity will be determined. An attempt will be made to clone the cDNAs for the AVP and CRF receptors using expression libraries and anti-idiotype antibodies. If necessary, the AVP receptor can be cloned using the oocyte expression system. Cloned probes will further the investigation of receptor regulation. In situ nucleic acid hybridization and S1 nuclease assay studies of pituitary AVP and CRF receptor modulation will be performed. Studies of these neuro-hormone receptors in degenerative brain diseases will be undertaken.